Lyme disease: Why does joint pain persist?

Researchers have found clues that might lead to a treatment for Lyme arthritis. The secret may lie in the walls of the bacterium that causes the condition.Ticks are responsible for spreading Lyme disease.

Lyme disease occurs when a person becomes infected with a tick-borne bacterium called Borrelia burgdorferi.

Although doctors can often treat Lyme disease with antibiotics, if they do not catch it early, the bacteria can cause long-term issues with the individual’s joints.

In fact, following infection with B. burgdorferi, about 60% of people develop a condition called Lyme arthritis, the hallmarks of which are inflamed and painful joints.

Lyme arthritis can persist for months or even years in some cases.

Researchers are still unsure why joint symptoms can continue long after antibiotics have destroyed the bacteria.

Lyme disease in numbers

Each year, the Centers for Disease Control and Prevention (CDC) receive reports of close to 30,000 cases of Lyme disease among the United States population.

However, the true number of cases is likely to be much higher. In fact, the CDC estimate that there might be up to 300,000 cases each year.

According to the CDC, reports of Lyme disease have tripled since the late 1990s, and overall, tick-borne diseases are becoming more prevalent. This increase is due, at least in part, to rising global temperatures.

Due to the steady growth in the number of cases, scientists are keen to uncover more effective ways of treating the long-term symptoms.

One researcher who has embarked on this mission is Brandon Jutras from Virginia Tech in Blacksburg. He and his team have the spent the last few years trying to understand what drives Lyme arthritis.

Among the scientists who contributed to the most recent work was Prof. Allen Steere, one of the doctors who discovered and named Lyme disease.

The researchers published their most recent findings in the journal Proceedings of the National Academy of Sciences of the United States of America.

Clues in cell walls

Specifically, the team wanted to understand why some cases of Lyme arthritis do not respond to treatment. For some people, even when there appears to be no obvious infection, symptoms persist.

As the authors write, “Excessive, dysregulated host immune responses are thought to play an important role in this outcome, but the underlying mechanisms are not completely understood.”

To investigate, they used samples that they had taken from people with Lyme disease who had not responded to antibiotic treatment.

They were interested in peptidoglycan (PG), a component of the protective layer that surrounds bacteria. Although most bacterial species synthesize PG, B. burgdorferi’s version of PG (PGBb) has unusual chemical features.

Additionally, most species of bacteria recycle their PG as they multiply, but B. burgdorferi do not have the enzymes necessary to reuse it. Instead, PGBb breaks off into fragments that remain floating free in the environment.

The scientists wondered whether these fragments might help explain why inflammation persists, even after antibiotics have eradicated the bacteria.

An immune response

The researchers showed that the immune system mounts a response to PGBb fragments. They found that markers of this immune activity were significantly higher in the synovial fluid from the participants’ joints than in their blood serum.

To further investigate, the scientists purified PGBb, making sure that they removed all other traces of the bacteria. Then, they injected the sample into mice. As expected, within just 24 hours, the animals’ joints became inflamed.

Jutras is keen to design interventions that can destroy PGBb in the joints of people with Lyme disease.

“This discovery will help researchers improve diagnostic tests and may lead to new treatment options for patients […] with Lyme arthritis.”

Lead author Brandon Jutras

The scientists hope that the findings will also be useful outside of Lyme arthritis, writing, “our finding that B. burgdorferi sheds immunogenic PGBb fragments during growth suggests a potential role for PGBb in the immunopathogenesis of other Lyme disease manifestations.”

Next, Jutras is hoping to develop a clearer picture of the chemistry of PGBb and understand how it can hang around in the tissues of the body for such long periods.

“We are interested in understanding everything associated with how patients respond, how we can prevent that response, and how we could possibly intervene with blocking therapies or therapies that eliminate the molecule entirely,” explains Jutras.

Designing a treatment based on these findings is still a long way in the future, but understanding more about how the condition manages to persist will certainly oil the wheels of future research. Scientists now have a new target to set their sights on. Read More